Dysbiosis individualizes fitness effect of antibiotic resistance in the mammalian gut

The fitness cost of antibiotic resistance in the absence of antibiotics is
crucial to the success of suspending antibiotics as a strategy to lower
resistance. Here we show that after antibiotic treatment the cost of
resistance within the complex ecosystem of the mammalian gut is
personalized. Using mice as an in vivo model, we find
that the fitness effect of the same resistant mutation can be deleterious
in a host, but neutral or even beneficial in other hosts. Such
antagonistic pleiotropy is shaped by the microbiota, as in germ-free
mice resistance is consistently costly across all hosts and in
hosts with similar microbiotas the host specific effect of resistance is
reduced. An eco-evolutionary model of competition for resources identifies
a general mechanism underlying between host variation and predicts that
the dynamics of compensatory evolution of resistant bacteria should be
host specific, a prediction that was supported by experimental
evolution in vivo. The microbiome of each human is close to
unique and our results suggest that the short-term costs of resistance and
its long-term within-host evolution will also be highly personalized, a
finding that may contribute to the observed variable outcome of
withdrawing antibiotics to reduce resistance levels.